Long non-coding RNA-AK138945 regulates myocardial ischemia-reperfusion injury via the miR-1-GRP94 signaling pathway

Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100μmol/L hydrogen peroxide(H_(2)O_(2)).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.

Growth differentiation factor 11 promotes macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway

Background:Myocardial infarctions(MI)is a major threat to human health especially in people exposed to cold environment.The polarization of macrophages towards different functional phenotypes(M1 macrophages and M2 macrophages)is closely related to MI repairment.The growth differentiation factor 11(GDF11)has been reported to play a momentous role in inflammatory associated diseases.In this study,we examined the regulatory role of GDF11 in macrophage polarization and elucidated the underlying mechanisms in MI.Methods:In vivo,the mice model of MI was induced by permanent ligation of the left anterior descending coronary artery(LAD),and mice were randomly divided into the sham group,MI group,and MI+GDF11 group.The protective effect of GDF11 on myocardial infarction and its effect on macrophage polarization were verified by echocardiography,triphenyl tetrazolium chloride staining and immunofluorescence staining of heart tissue.In vitro,based on the RAW264.7 cell line,the effect of GDF11 in promoting macrophage polarization toward the M2 type by inhibiting the Notch1 Signaling pathway was validated by qRT-PCR,Western blot,and flow cytometry.Results:We found that GDF11 was significantly downregulated in the cardiac tissue of MI mice.And GDF11 supplementation can improve the cardiac function.Moreover,GDF11 could reduce the proportion of M1 macrophages and increase the accumulation of M2 macrophages in the heart tissue of MI mice.Furthermore,the cardioprotective effect of GDF11 on MI mice was weakened after macrophage clearance.At the cellular level,application of GDF11 could inhibit the expression of M1 macrophage(classically activated macrophage)markers iNOS,interleukin(IL)-1β,and IL-6 in a dose-dependent manner.In contrast,GDF11 significantly increased the level of M2 macrophage markers including IL-10,CD206,arginase 1(Arg1),and vascular endothelial growth factor(VEGF).Interestingly,GDF11 could promote M1 macrophages polarizing to M2 macrophages.At the molecular level,GDF11 significantly down-regulated the Notch1 signaling pathway,the activation of which has been demonstrated to promote M1 polarization in macrophages.Conclusions:GDF11 promoted macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway.

The effect of the beam shapes on the doubly-clamped piezoelectric energy harvester

For a piezoelectric energy harvester composed of a doubly-clamped beam with arbitrary width shapes and a proof mass, the influence of beam shapes and electrode arrangements on different electric outputs is analyzed. The output performances of piezoelectric energy harvesters with rectangular shape, concave trapezoidal shape, and concave parabolic shape are compared, and an optimization way is given. The experimental results validate the effectiveness of the methods.

Multilocus DNA metabarcoding diet analyses of small cetaceans:a case study on highly vulnerable humpback dolphins and finless porpoises from the Pearl River Estuary,China

Accurate diet identification of top predators is crucial to fully understand their ecological roles.Compared to terrestrial animals,gathering dietary information from cetaceans is notoriously difficult.Here,we applied a multilocus metabarcoding approach to investigate the diet of vulnerable Indo-Pacific humpback dolphins and Indo-Pacificfinless porpoises from the Pearl River Estuary(PRE),China.Our analyses identified 21 preyfish species from the 42 humpback dolphin stomachs,as well as 10 species offish and 1 species of cephalopod from the 13finless porpoise stomachs.All of the taxa were assigned to the species level,highlighting that the multimarker approach could facilitate species identification.Most of the prey species were small-and medium-sizedfishes that primarily fed on zooplankton.The calculated similarity index revealed a moderated dietary overlap between the 2 cetaceans,presumably due to the feeding of the 2 predators in association withfishing vessels in the PRE.A more diverse diet was observed in humpback dolphins in the closedfishing season compared to thefishing season,implying the influence on the dolphin diet due to the availability of commercialfishery resources.However,according to the results of species rarefaction curves,ourfindings on the feeding habits of the 2 cetaceans are still limited by insufficient sample size and therefore should be interpreted with caution.This study represents afirst attempt to apply the multilocus DNA metabarcoding technique in the diet analysis of small cetaceans,although more efforts are needed to improve this type of analysis.

Social media study of public opinions on potential COVID-19 vaccines: informing dissent, disparities, and dissemination

Background The current development of vaccines for severe acute respiratory syndrome coronavirus 2(SARSCoV-2)is unprecedented.Little is known,however,about the nuanced public opinions on the vaccines on social media.Methods We adopted a human-guided machine learning framework using more than six million tweets from almost two million unique Twitter users to capture public opinions on the vaccines for SARS-CoV-2,classifying them into three groups:pro-vaccine,vaccine-hesitant,and anti-vaccine.After feature inference and opinion mining,10,945 unique Twitter users were included in the study population.Multinomial logistic regression and counterfactual analysis were conducted.Results Socioeconomically disadvantaged groups were more likely to hold polarized opinions on coronavirus disease 2019(COVID-19)vaccines,either pro-vaccine(B=0.40,SE=0.08,P<0.001,OR=1.49;95%CI=1.26-1.75)or anti-vaccine(B=0.52,SE=0.06,P<0.001,OR=1.69;95%CI=1.49-1.91).People who have the worst personal pandemic experience were more likely to hold the anti-vaccine opinion(B=−0.18,SE=0.04,P<0.001,OR=0.84;95%CI=0.77-0.90).The United States public is most concerned about the safety,effectiveness,and political issues regarding vaccines for COVID-19,and improving personal pandemic experience increases the vaccine acceptance level.